Immunogenicity and safety of an inactivated SARS-CoV-2 vaccine (Sinopharm BBIBP-CorV) coadministered with quadrivalent split-virion inactivated influenza vaccine and 23-valent pneumococcal polysaccharide vaccine in China: A multicentre, non-inferiority, open-label, randomised, controlled, phase 4 trial

Haiping Chen, Zhuoying Huang, Shaoying Chang, Mei Hu, Qingbin Lu, Yuntao Zhang, Hui Wang, Yanhui Xiao, Hui Wang, Yonghong Ge, Yong Zou, Fuqiang Cui, Shasha Han, Min Zhang, Shengyi Wang, Xiaoping Zhu, Biao Zhang, Zhi Li, Jia Ren, Xiao Chen, Rui Ma, Lei Zhang, Xue Guo, Linyun Luo, Xiaodong Sun, Xiaoming Yang, Haiping Chen, Zhuoying Huang, Shaoying Chang, Mei Hu, Qingbin Lu, Yuntao Zhang, Hui Wang, Yanhui Xiao, Hui Wang, Yonghong Ge, Yong Zou, Fuqiang Cui, Shasha Han, Min Zhang, Shengyi Wang, Xiaoping Zhu, Biao Zhang, Zhi Li, Jia Ren, Xiao Chen, Rui Ma, Lei Zhang, Xue Guo, Linyun Luo, Xiaodong Sun, Xiaoming Yang

Abstract

Background: The safety and immunogenicity of the coadministration of an inactivated SARS-CoV-2 vaccine (Sinopharm BBIBP-CorV), quadrivalent split-virion inactivated influenza vaccine (IIV4), and 23-valent pneumococcal polysaccharide vaccine (PPV23) in adults in China is unknown.

Methods: In this open-label, non-inferiority, randomised controlled trial, participants aged ≥ 18 years were recruited from the community. Individuals were eligible if they had no history of SARS-CoV-2 vaccine or any pneumonia vaccine and had not received an influenza vaccine during the 2020-21 influenza season. Eligible participants were randomly assigned (1:1:1), using block randomization stratified, to either: SARS-CoV-2 vaccine and IIV4 followed by SARS-CoV-2 vaccine and PPV23 (SARS-CoV-2 + IIV4/PPV23 group); two doses of SARS-CoV-2 vaccine (SARS-CoV-2 vaccine group); or IIV4 followed by PPV23 (IIV4/PPV23 group). Vaccines were administered 28 days apart, with blood samples taken on day 0 and day 28 before vaccination, and on day 56.

Results: Between March 10 and March 15, 2021, 1152 participants were recruited and randomly assigned to three groups (384 per group). 1132 participants were included in the per-protocol population (375 in the SARS-CoV-2 + IIV4/PPV23 group, 380 in the SARS-CoV-2 vaccine group, and 377 in the IIV4/PPV23 group). The seroconversion rate (100 % vs 100 %) and GMT (159.13 vs 173.20; GMT ratio of 0.92 [95 % CI 0.83 to 1.02]) of SARS-CoV-2 neutralising antibodies in the SARS-CoV-2 + IIV4/PPV23 group was not inferior to those in the SARS-CoV-2 vaccine group. The SARS-CoV-2 + IIV4/PPV23 group was not inferior to the IIV4/PPV23 group in terms of seroconversion rates and GMT of influenza virus antibodies for all strains except for the seroconversion rate for the B/Yamagata strain. The SARS-CoV-2 + IIV4/PPV23 group was not inferior to the IIV4/PPV23 group regarding seroconversion rates and GMC of Streptococcus pneumoniae IgG antibodies specific to all serotypes. All vaccines were well tolerated.

Conclusions: The coadministration of the inactivated SARS-CoV-2 vaccine and IIV4/PPV23 is safe with satisfactory immunogenicity. This study is registered with ClinicalTrials.gov, NCT04790851.

Keywords: 23-valent pneumococcal polysaccharide vaccine; Coadministration; Inactivated SARS-CoV-2 vaccine; Split-virion inactivated influenza vaccine.

Conflict of interest statement

Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Xiaoming Yang is the employee of the China National Biotec Group, receives the grant from National Program on Key Research Project of China (2020YFC0842100) during the conduct of the study, and has four authorized patents of ZL202010559132.3, ZL202010645875.2, ZL202010537733.4 and ZL202010537730.0. Yuntao Zhang is the employee of the China National Biotec Group, receives the grant from The National Key Research and Development Project of China (2020YFC0842100) during the conduct of the study. Hui Wang is the employee of the Beijing Institute of Biological Products, receives the grants from The National Key Research and Development Project of China (2020YFC0842100) and the Beijing Municipal Science & Technology Commission (Z201100005420014) during the conduct of the study and has three authorized patents of ZL202010645875.2, ZL202010537733.4 and ZL202010537730.0, two pending patents of 202110052921.2 and 202110052933.5. Rui Ma is the employee of the Beijing Institute of Biological Products, receives the grant from The National Key Research and Development Project of China (2020YFC0842100) during the conduct of the study. Haiping Chen, Yanhui Xiao, Shasha Han, Min Zhang, Shengyi Wang and Linyun Luo are the employees of the China National Biotec Group. Yonghong Ge and Lei Zhang are the employees of the Chengdu Institute of Biological Products. Yong Zou and Xue Guo are the employees of the Changchun Institute of Biological Products. All other authors report no potential conflicts.

Copyright © 2022 Elsevier Ltd. All rights reserved.

Figures

Fig. 1
Fig. 1
Trial profile. IIV4 = quadrivalent split-virion inactivated influenza vaccine. PPV23 = 23-valent pneumococcal polysaccharide vaccine. S pneumoniae = Streptococcus pneumoniae.
Fig. 2
Fig. 2
Seroconversion rate and GMT of SARS-CoV-2 neutralising antibodies. The left bar chart shows the seroconversion rates (%) of neutralising antibodies with error bars showing 95 % CIs. The comparisons between the groups among all the participants found SARS-COV-2 + IIV4/PPV23 group to be non-inferior to SARS-CoV-2 vaccine (p < 0·025). The right plot shows the post-vaccination GMT of SARS-CoV-2 neutralising antibodies and the error bars showing 95 % CIs. SARS-COV-2 + IIV4/PPV23 group was non-inferior to SARS-CoV-2 vaccine only (p < 0·025). The pre-vaccination GMT of the SARS-CoV-2 neutralising antibodies was 2 (95 % CI 2–2). GMT = geometrical mean titre. IIV4 = quadrivalent split-virion inactivated influenza vaccine. PPV23 = 23-valent pneumococcal polysaccharide vaccine.
Fig. 3
Fig. 3
Seroconversion rate and GMT of influenza virus antibodies on day 28. The left bar chart shows the seroconversion rates (%) of influenza virus antibodies and error bars show the 95 % CIs. For each strain, SARS-COV-2 + IIV4/PPV23 group was non-inferior to IIV4/PPV23 group (except for B/Yamagata on day 28: p = 0·080). The right plot shows the post-vaccination GMT of influenza virus antibodies and the error bars show the 95 % CIs. For all strains, SARS-COV-2 + IIV4/PPV23 group was non-inferior to IIV4/PPV23 group (both p < 0.025 ). GMT = geometrical mean titre. IIV4 = quadrivalent split-virion inactivated influenza vaccine. PPV23 = 23-valent pneumococcal polysaccharide vaccine.
Fig. 4
Fig. 4
Seroconversion rate and GMC of S pneumoniae IgG antibodies on day 56. The left bar chart shows the seroconversion rates (%) of the S pneumoniae IgG antibodies and the error bars show the 95 % CIs. For all serotypes, SARS-COV-2 + IIV4/PPV23 group was non-inferior to IIV4/PPV23 group (all p < 0.025 ). GMC = geometric mean concentration. IIV4 = quadrivalent split-virion inactivated influenza vaccine. PPV23 = 23-valent pneumococcal polysaccharide vaccine. S pneumoniae = Streptococcus pneumoniae.

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